Two sex pheromone receptors for sexual communication in the American cockroach.

Volatile sex pheromones are vital for sexual communication between males and females. Females of the American cockroach, Periplaneta americana, produce and emit two sex pheromone components, periplanone-A (PA) and periplanone-B (PB). Although PB is the major sex attractant and can attract males, how it interacts with PA in regulating sexual behaviors is still unknown. In this study, we found that in male cockroaches, PA counteracted PB attraction. We identified two odorant receptors (ORs), OR53 and OR100, as PB/PA and PA receptors, respectively. OR53 and OR100 were predominantly expressed in the antennae of sexually mature males, and their expression levels were regulated by the sex differentiation pathway and nutrition-responsive signals. Cellular localization of OR53 and OR100 in male antennae further revealed that two types of sensilla coordinate a complex two-pheromone-two-receptor pathway in regulating cockroach sexual behaviors. These findings indicate distinct functions of the two sex pheromone components, identify their receptors and possible regulatory mechanisms underlying the male-specific and age-dependent sexual behaviors, and can guide novel strategies for pest management.

Sex-Specific and State-Dependent Neuromodulation Regulates Male and Female Locomotion and Sexual Behaviors.

Males and females display dimorphic behaviors that often involve sex-specific locomotor patterns. How the sexually dimorphic locomotion is mediated is poorly understood. In this study, we identify a neuropeptide that oppositely regulates locomotion for efficient sexual behaviors in Drosophila males and females. We find that males are less active than females if isolated. However, when sexually aroused through activating homologous but sexually dimorphic pC1 neurons, males exhibit higher activity levels than females. We discover diuretic hormone 44 (DH44) that functions in pC1 neurons in a sex-specific way to inhibit male locomotion and promote female locomotion. Surprisingly, DH44 exerts opposite effects in sexually aroused flies to promote male locomotion and suppress female locomotion, which is crucial for successful male courtship and female receptivity. These findings demonstrate sexually dimorphic and state-dependent control of locomotor activity by pC1 neuronal activity and DH44 modulation.

A neural pathway for social modulation of spontaneous locomotor activity (SoMo-SLA) in Drosophila.

Social enrichment or social isolation affects a range of innate behaviors, such as sex, aggression, and sleep, but whether there is a shared mechanism is not clear. Here, we report a neural mechanism underlying social modulation of spontaneous locomotor activity (SoMo-SLA), an internal-driven behavior indicative of internal states. We find that social enrichment specifically reduces spontaneous locomotor activity in male flies. We identify neuropeptides Diuretic hormone 44 (DH44) and Tachykinin (TK) to be up- and down-regulated by social enrichment and necessary for SoMo-SLA. We further demonstrate a sexually dimorphic neural circuit, in which the male-specific P1 neurons encoding internal states form positive feedback with interneurons coexpressing doublesex (dsx) and Tk to promote locomotion, while P1 neurons also form negative feedback with interneurons coexpressing dsx and DH44 to inhibit locomotion. These two opposing neuromodulatory recurrent circuits represent a potentially common mechanism that underlies the social regulation of multiple innate behaviors.

The Mediator kinase module enhances polymerase activity to regulate transcriptional memory after heat stress in Arabidopsis.

Plants are often exposed to recurring adverse environmental conditions in the wild. Acclimation to high temperatures entails transcriptional responses, which prime plants to better withstand subsequent stress events. Heat stress (HS)-induced transcriptional memory results in more efficient re-induction of transcription upon recurrence of heat stress. Here, we identified CDK8 and MED12, two subunits of the kinase module of the transcription co-regulator complex, Mediator, as promoters of heat stress memory and associated histone modifications in Arabidopsis. CDK8 is recruited to heat-stress memory genes by HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2). Like HSFA2, CDK8 is largely dispensable for the initial gene induction upon HS, and its function in transcriptional memory is thus independent of primary gene activation. In addition to the promoter and transcriptional start region of target genes, CDK8 also binds their 3'-region, where it may promote elongation, termination, or rapid re-initiation of RNA polymerase II (Pol II) complexes during transcriptional memory bursts. Our work presents a complex role for the Mediator kinase module during transcriptional memory in multicellular eukaryotes, through interactions with transcription factors, chromatin modifications, and promotion of Pol II efficiency.

Miniaturized and highly-sensitive fiber-optic photoacoustic gas sensor based on an integrated tuning fork by mechanical processing with dual-prong differential measurement.

A proof-of-concept gas sensor based on a miniaturized and integrated fiber-optic photoacoustic detection module was introduced and demonstrated for the purpose of developing a custom tuning-fork (TF)-enhanced photoacoustic gas sensor. Instead of piezoelectric quartz tuning fork (QTF) in conventional quartz-enhanced photoacoustic spectroscopy (QEPAS), a low-cost custom aluminum alloy TF fabricated by mechanical processing was employed as a photoacoustic transducer and the vibration of TF was measured by fiber-optic Fabry-Pérot (FP) interferometer (FPI). The mechanical processing-based TF design scheme greatly increases the flexibility of the TF design with respect to the complex and expensive manufacture process of custom QTFs, and thus it can be better exploited to detect gases with slow vibrational-translational (V-T) relaxation rates and combine with light sources with poor beam quality. The resonance frequency and the quality factor of the designed custom TF at atmospheric pressure were experimentally determined to be 7.3 kHz and 4733, respectively. Dual-prong differential measurement method was proposed to double the photoacoustic signal and suppress the external same-direction noise. After detailed optimizing and investigating for the operating parameters by measuring H2O, the feasibility of the developed sensor for gas detection was demonstrated with a H2O minimum detection limit (MDL) of 1.2 ppm, corresponding to a normalized noise equivalent absorption (NNEA) coefficient of 3.8 × 10-8 cm-1 W/Hz1/2, which are better than the QTF-based photoacoustic sensors. The proposed gas sensing approach combined the advantages of QEPAS and fiber-optic sensing, which can greatly expand the application domains of PAS-based gas sensors.

All-optical non-resonant photoacoustic spectroscopy for multicomponent gas detection based on aseismic photoacoustic cell.

An all-optical non-resonant photoacoustic spectroscopy system for multicomponent gas detection based on a silicon cantilever optical microphone (SCOM) and an aseismic photoacoustic cell is proposed and demonstrated. The SCOM has a high sensitivity of over 96.25 rad/Pa with sensitivity fluctuation less than ± 1.56 dB between 5 Hz and 250 Hz. Besides, the minimal detectable pressure (MDP) of the sensor is 0.55 µPa·Hz-1/2 at 200 Hz, which indicates that the fabricated sensor has high sensitivity and low noise level. Six different gases of CO2, CO, CH4, C2H6, C2H4, C2H2 are detected at the frequency of 10 Hz, whose detection limits (3σ) are 62.66 ppb, 929.11 ppb, 1494.97 ppb, 212.94 ppb, 1153.36 ppb and 417.61 ppb, respectively. The system achieves high sensitivity and low detection limits for trace gas detection. In addition, the system exhibits seismic performance with suppressing vibration noise by 4.5 times, and achieves long-term stable operation. The proposed non-resonant all-optical PAS multi-component gas detection system exhibits the advantages of anti-vibration performance, low gas consumption and long term stability, which provides a solution for working in complex environments with inherently safe.

A neural pathway underlying hunger modulation of sexual receptivity in Drosophila females.

Accepting or rejecting a mate is one of the most crucial decisions a female will make, especially when faced with food shortage. Previous studies have identified the core neural circuity from sensing male courtship or mating status to decision-making for sexual receptivity in Drosophila females, but how hunger and satiety states modulate female receptivity is poorly understood. Here, we identify the neural circuit and its neuromodulation underlying the hunger modulation of female receptivity. We find that adipokinetic hormone receptor (AkhR)-expressing neurons inhibit sexual receptivity in a starvation-dependent manner. AkhR neurons are octopaminergic and act on a subset of Octß1R-expressing LH421 neurons. Knocking down Octß1R expression in LH421 neurons eliminates starvation-induced suppression of female receptivity. We further find that LH421 neurons inhibit the sex-promoting pC1 neurons via GABA-resistant to dieldrin (Rdl) signaling. pC1 neurons also integrate courtship stimulation and mating status and thus serve as a common integrator of multiple internal and external cues for decision-making.

Asexuality in Drosophila juvenile males is organizational and independent of juvenile hormone.

Sexuality is generally prevented in newborns and arises with organizational rewiring of neural circuitry and optimization of fitness for reproduction competition. Recent studies reported that sex circuitry in Drosophila melanogaster is developed in juvenile males but functionally inhibited by juvenile hormone (JH). Here, we find that the fly sex circuitry, mainly expressing the male-specific fruitless (fruM ) and/or doublesex (dsx), is organizationally undeveloped and functionally inoperative in juvenile males. Artificially activating all fruM neurons induces substantial courtship in solitary adult males but not in juvenile males. Synaptic transmissions between major courtship regulators and all dsx neurons are strong in adult males but either weak or undetectable in juvenile males. We further find that JH does not inhibit male courtship in juvenile males but instead promotes courtship robustness in adult males. Our results indicate that the transition to sexuality from juvenile to adult flies requires organizational rewiring of neural circuitry.

Integrating lipid metabolism, pheromone production and perception by Fruitless and Hepatocyte Nuclear Factor 4.

Sexual attraction and perception are crucial for mating and reproductive success. In Drosophila melanogaster, the male-specific isoform of Fruitless (Fru), FruM, is a known master neuro-regulator of innate courtship behavior to control the perception of sex pheromones in sensory neurons. Here, we show that the non-sex-specific Fru isoform (FruCOM) is necessary for pheromone biosynthesis in hepatocyte-like oenocytes for sexual attraction. Loss of FruCOM in oenocytes resulted in adults with reduced levels of cuticular hydrocarbons (CHCs), including sex pheromones, and show altered sexual attraction and reduced cuticular hydrophobicity. We further identify Hepatocyte nuclear factor 4 (Hnf4) as a key target of FruCOM in directing fatty acid conversion to hydrocarbons. Fru or Hnf4 depletion in oenocytes disrupts lipid homeostasis, resulting in a sex-dimorphic CHC profile that differs from doublesex- and transformer-dependent CHC dimorphism. Thus, Fru couples pheromone perception and production in separate organs to regulate chemosensory communications and ensure efficient mating behavior.

Integrating lipid metabolism, pheromone production and perception by Fruitless and Hepatocyte nuclear factor 4.

Sexual attraction and perception, governed by separate genetic circuits in different organs, are crucial for mating and reproductive success, yet the mechanisms of how these two aspects are integrated remain unclear. In Drosophila , the male-specific isoform of Fruitless (Fru), Fru M , is known as a master neuro-regulator of innate courtship behavior to control perception of sex pheromones in sensory neurons. Here we show that the non-sex specific Fru isoform (Fru COM ) is necessary for pheromone biosynthesis in hepatocyte-like oenocytes for sexual attraction. Loss of Fru COM in oenocytes resulted in adults with reduced levels of the cuticular hydrocarbons (CHCs), including sex pheromones, and show altered sexual attraction and reduced cuticular hydrophobicity. We further identify Hepatocyte nuclear factor 4 ( Hnf4 ) as a key target of Fru COM in directing fatty acid conversion to hydrocarbons in adult oenocytes. fru - and Hnf4 -depletion disrupts lipid homeostasis, resulting in a novel sex-dimorphic CHC profile, which differs from doublesex - and transformer -dependent sexual dimorphism of the CHC profile. Thus, Fru couples pheromone perception and production in separate organs for precise coordination of chemosensory communication that ensures efficient mating behavior. Teaser: Fruitless and lipid metabolism regulator HNF4 integrate pheromone biosynthesis and perception to ensure robust courtship behavior.

Public opinion changing patterns under the double-hazard scenario of natural disaster and public health event.

In the context of the COVID-19 epidemic, a "double-hazard scenario" consisting of a natural disaster and a public health event occurring simultaneously is likely to arise. Focusing on this double-hazard scenario, this study developed a new opinion dynamics model that verifies the effect of opinion dynamic in practical applications and extends the realistic meaning of the logic matrix. The new model can be used to quickly identify changing trends in public opinion about two co-occurring public safety events in China, helping the government to better anticipate and respond to these real double-hazard scenarios. The new model was tested with three real double-hazard scenarios involving natural disasters and public health events in China and the simulation results were analyzed. Using visualization and Pearson correlation coefficients to analyze more than a million items of network-wide public opinion data, the new model was found to show a good fit with reality. The study finally found that in China, public attention to both natural hazards and public health events was greater when these public safety events co-occurred (double-hazard scenario) than when they occurred separately (single-hazard scenarios). These results verify the coupling phenomenon of different disasters in a multi-hazard scenario at the information level for the first time, which is greatly meaningful for multi-hazard research.

Combined effect of stimulation and electromagnetic induction on absence seizure inhibition in coupled thalamocortical circuits.

Deep brain stimulation (DBS) and electromagnetic induction are new techniques that are increasingly used in modern epilepsy treatments; however, the mechanism of action remains unclear. In this study, we constructed a bidirectional-coupled cortico-thalamic model, based on which we proposed three regulation schemes: isolated regulation of DBS, isolated regulation of electromagnetic induction and combined regulation of the previous two. In particular, we introduced DBS with a lower amplitude and considered the influence of electromagnetic induction caused by the transmembrane current on the membrane potential. The most striking finding of this study is that the three therapeutic schemes could effectively control abnormal discharge, and combined regulation could reduce the occurrence of epileptic seizures more effectively. The present study bridges the gap between the bidirectional coupling model and combined control. In this way, the damage induced by electrical stimulation of the patient's brain tissue could be reduced, and the abnormal physiological discharge pattern of the cerebral cortex was simultaneously regulated by different techniques. This work opens new avenues for improving brain dysfunction in patients with epilepsy, expands ideas for promoting the development of neuroscience and is meaningful for improving the health of modern society and developing the field of science.

All-optical light-induced thermoacoustic spectroscopy for remote and non-contact gas sensing.

All-optical light-induced thermoacoustic spectroscopy (AO-LITS) is reported for the first time for highly sensitive and selective gas sensing, in which a commercial standard quartz tuning fork (QTF) is employed as a photothermal detector. The vibration of the QTF was measured by the highly sensitive fiber-optic Fabry-Pérot (FP) interferometry (FPI) technique, instead of the piezoelectric detection in the conventional LITS. To improve the stability of the sensor system, a compact QTF-based fiber-optic FPI module is fabricated by 3D printing technique and a dual-wavelength demodulation method with the ellipse-fitting differential-cross-multiplication algorithm (DW-EF-DCM) is exploited for the FPI measurement. The all-optical detection scheme has the advantages of remote detection and immunity to electromagnetic interference. A minimum detection limit (MDL) of 422 ppb was achieved for hydrogen sulfide (H2S), which was ~ 3 times lower than a conventional electrical LITS sensor system. The AO-LITS can provide a promising approach for remote and non-contact gas sensing in the whole infrared spectral region.

Small-volume highly-sensitive all-optical gas sensor using non-resonant photoacoustic spectroscopy with dual silicon cantilever optical microphones.

A small-volume highly-sensitive photoacoustic spectroscopy (PAS) methane detection system based on differential silicon cantilever optical microphones (SCOMs) is proposed and experimentally demonstrated. The system contains a compact non-resonant photoacoustic cell with a small volume of 1.2 mL and symmetrically-located dual SCOMs, as well as a distributed feedback laser at 1650.96 nm. The two identical SCOMs utilize the Fabry-Perot interferometric fiber-optic structure, with the differential Q-point demodulation algorithm to suppress the external vibration noise. Experimental results show that the SCOM has a high displacement sensitivity about 7.1 µm/Pa at 150 Hz and within 2.5 dB fluctuation between 5 Hz and 250 Hz. In the PAS gas sensing experiment, the normalized noise equivalent absorption coefficient of the PAS system is estimated to be 1.2 × 10-9 cm-1·W·Hz-1/2 and the minimum detection limit for methane is about 111.2 ppb with 1 s integration time. External disturbance is also applied to the dual SCOM system and results show excellent stability and noise resistance. The proposed PAS system exhibits superiorities of low gas consumption, high sensitivity and immunity to vibration and electromagnetic interference, which has an enormous potential in medicine, industry and environment.

The doublesex gene regulates dimorphic sexual and aggressive behaviors in Drosophila.

Most animal species display dimorphic sexual behaviors and male-biased aggressiveness. Current models have focused on the male-specific product from the fruitless (fruM) gene, which controls male courtship and male-specific aggression patterns in fruit flies, and describe a male-specific mechanism underlying sexually dimorphic behaviors. Here we show that the doublesex (dsx) gene, which expresses male-specific DsxM and female-specific DsxF transcription factors, functions in the nervous system to control both male and female sexual and aggressive behaviors. We find that Dsx is not only required in central brain neurons for male and female sexual behaviors, but also functions in approximately eight pairs of male-specific neurons to promote male aggressiveness and approximately two pairs of female-specific neurons to inhibit female aggressiveness. DsxF knockdown females fight more frequently, even with males. Our findings reveal crucial roles of dsx, which is broadly conserved from worms to humans, in a small number of neurons in both sexes to establish dimorphic sexual and aggressive behaviors.

Monocarboxylate transporter upregulation in induced regulatory T cells promotes resistance to anti-PD-1 therapy in hepatocellular carcinoma patients.

Background: Programmed cell death-1 (PD-1) immune checkpoint inhibitors are not effective in treating all patients with hepatocellular carcinoma (HCC), and regulatory T cells (Tregs) may determine the resistance to anti-PD-1 therapy. Methods: Patients were divided into two groups based on the clinical efficacy of anti-PD-1 therapy. Flow cytometry was used to determine the phenotype of CD4+, CD8+, and Tregs in peripheral blood mononuclear cells (PBMCs). CD4+CD45RA+T cells were sorted to analyze Treg differentiation and function. Results: No significant differences were found between resistant and sensitive patients in the percentage of CD4+ T cells and Tregs in PBMCs or the differentiation and function of induced Tregs (iTregs). However, iTregs from resistant patients presented higher monocarboxylate transporter (MCT) expression. Lactate induced more iTregs and improved OXPHOS levels in the resistant group. MCT1 and MCT2 were highly expressed in tumor-infiltrating Tregs, and patients with higher MCT1 expression had worse clinical outcomes. Combinatorial therapy with MCT antibody and anti-PD-1 therapy effectively inhibited tumor growth. Conclusion: MCT and its downstream lactate signal in Tregs can confer anti-PD-1 resistance and may be a marker of poor prognosis in HCC.

Role of coupling distances in a coupled thalamocortical network in the treatment of epilepsy.

The establishment of a recent theoretical model of a coupled cortical thalamic network is an important step in the spatiotemporal dynamics of the brain. However, choosing the coupling distances and parameters for deep brain stimulation remains a very challenging task. This study aimed to establish a coupled cortical thalamic model with uncertain coupling distances. Utilizing different pathways formed by the pyramidal neuronal population, thalamic reticular nucleus, and thalamic relay nucleus, we reduced epileptic seizures with spike-wave discharges (SWDs) at 2-4 Hz. In modelling terms, numerical simulations demonstrated that a combination (1/3, 1/9) of the left and right ventricles is the optimal coupling distance of the proposed model by analyzing the percentage of SWDs. In simulation terms, on the one hand, the number of SWDs is inversely proportional to the amplitude; on the other hand, the number of SWDs shows a U-shaped trend with the change in frequency. The present study provides an important theoretical basis and direction for the future treatment of absence epilepsy. In brief, our simulation results will hopefully provide some help to patients.

A male-specific doublesex isoform reveals an evolutionary pathway of sexual development via distinct alternative splicing mechanisms.

The doublesex/mab-3 related transcription factor (Dmrt) genes regulate sexual development in metazoans. Studies of the doublesex (dsx) gene in insects, in particular Drosophila melanogaster, reveal that alternative splicing of dsx generates sex-specific Dsx isoforms underlying sexual differentiation. Such a splicing-based mechanism underlying sex-specific Dmrt function is thought to be evolved from a transcription-based mechanism used in non-insect species, but how such transition occurs during evolution is not known. Here we identified a male-specific dsx transcript (dsxM2) through intron retention (IR), in addition to previously identified dsxM and dsxF transcripts through alternative polyadenylation (APA) with mutually exclusive exons. We found that DsxM2 had similarly masculinizing function as DsxM. We also found that the IR-based mechanism generating sex-specific dsx transcripts was conserved from flies to cockroaches. Further analysis of these dsx transcripts suggested an evolutionary pathway from sexually monomorphic to sex-specific dsx via the sequential use of IR-based and APA-based alternative splicing.

A single gene integrates sex and hormone regulators into sexual attractiveness.

Sex differentiation and hormones are essential for the development of sexual signals in animals, and the regulation of sexual signals involves complex gene networks. However, it is unknown whether a core gene is able to connect the upstream regulators for controlling sexual signal outputs and behavioural consequences. Here, we identify a single gene that integrates both sex differentiation and hormone signalling with sexual attractiveness in an insect model. CYP4PC1 in the German cockroach, Blattella germanica, controls the rate-limiting step in producing female-specific contact sex pheromone (CSP) that stimulates male courtship. As revealed by behavioural, biochemical, molecular, genetic and bioinformatic approaches, in sexually mature females, CYP4PC1 expression and CSP production are coordinately induced by sex differentiation genes and juvenile hormone (JH) signalling. In adult males, direct inhibition of CYP4PC1 expression by doublesexM binding in gene promoter and lack of the gonadotropic hormone JH prevent CSP production, thus avoiding male-male attraction. By manipulating the upstream regulators, we show that wild-type males prefer to court cockroaches with higher CYP4PC1 expression and CSP production in a dose-dependent manner, regardless of their sex. These findings shed light on how sex-specific and high sexual attractiveness is conferred in insects.

AIEgen Intercalated Nanoclay-Based Photodynamic/Chemodynamic Theranostic Platform for Ultra-Efficient Bacterial Eradication and Fast Wound Healing.

With the emergence and global spread of bacterial resistance, pathogenic bacterial infections have become a serious threat to human health. Thus, therapeutic strategies with highly antibacterial efficacy and a low tendency to induce drug resistance are strongly desired to combat bacterial infections. Here, an ultra-efficient photodynamic/chemodynamic theranostics platform is developed by intercalating an aggregation-induced emission (AIE) photosensitizer, TPCI, into the nanolayers of iron-bearing montmorillonite (MMT). The formed TPCI/MMT composite can not only perform efficient photodynamic therapy (PDT) through a burst generation of singlet oxygen (1O2) upon white light illumination but also continuously implement chemodynamic therapy (CDT) by converting endogenous hydrogen peroxide into highly toxic hydroxyl radicals (•OH) due to iron release. In addition, the fluorescence of TPCI/MMT can be activated due to the AIE feature of TPCI, which helps guide the location of the antimicrobials. The combination of such powerful bombs (PDT) and unremitting ambushes (CDT) in TPCI/MMT can synergistically and effectively eliminate bacteria and promote faster wound healing in vivo with good biocompatibility and low side effects. The smart and simple design of TPCI/MMT provides a representative paradigm for achieving efficient antimicrobials to combat the coming resistance crisis.